AIMS: Rituximab is a monoclonal antibody directed against CD20, which is approved in rheumatoid arthritis (RA). This study aimed at assessing the influence of CD19+ cell counts as target-antigen amount, and of immunoglobulin G (IgG) serum concentrations on rituximab pharmacokinetics in RA patients. METHODS: In a cohort of 64 RA patients who had received repetitive courses of rituximab, the influence of CD19+ cell count, IgG serum concentration, body surface area, sex and disease activity score in 28 joints on rituximab pharmacokinetic parameters was assessed using a population pharmacokinetic analysis. RESULTS: A two-compartment model, with first-order distribution and elimination best described the data. The volume of distribution of central compartment and clearance of rituximab were estimated at 4.7 l and 0.56 l day-1 , respectively. Distribution and elimination half-lives were 0.9 days and 17.3 days, respectively. As expected, the central volume of distribution increased with body surface area (P = 0.012) and was higher in male than in female (P = 0.004). We found that the elimination rate constant (k10 ) increased with CD19+ count (P = 0.00022) and IgG concentration (P = 7.4 × 10-8 ), and that k10 decreased with time (P = 0.00015), partly explained by a change in target-antigen amount. CONCLUSIONS: The association between CD19+ count and k10 may be explained by target-mediated drug disposition, while the association between IgG serum concentration and k10 may be explained by a saturation of the neonatal Fc receptor at high IgG concentrations, resulting in decreased recycling of rituximab.
AIMS: Rituximab is a monoclonal antibody directed against CD20, which is approved in rheumatoid arthritis (RA). This study aimed at assessing the influence of CD19+ cell counts as target-antigen amount, and of immunoglobulin G (IgG) serum concentrations on rituximab pharmacokinetics in RApatients. METHODS: In a cohort of 64 RApatients who had received repetitive courses of rituximab, the influence of CD19+ cell count, IgG serum concentration, body surface area, sex and disease activity score in 28 joints on rituximab pharmacokinetic parameters was assessed using a population pharmacokinetic analysis. RESULTS: A two-compartment model, with first-order distribution and elimination best described the data. The volume of distribution of central compartment and clearance of rituximab were estimated at 4.7 l and 0.56 l day-1 , respectively. Distribution and elimination half-lives were 0.9 days and 17.3 days, respectively. As expected, the central volume of distribution increased with body surface area (P = 0.012) and was higher in male than in female (P = 0.004). We found that the elimination rate constant (k10 ) increased with CD19+ count (P = 0.00022) and IgG concentration (P = 7.4 × 10-8 ), and that k10 decreased with time (P = 0.00015), partly explained by a change in target-antigen amount. CONCLUSIONS: The association between CD19+ count and k10 may be explained by target-mediated drug disposition, while the association between IgG serum concentration and k10 may be explained by a saturation of the neonatal Fc receptor at high IgG concentrations, resulting in decreased recycling of rituximab.
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Authors: R M Thurlings; O Teng; K Vos; D M Gerlag; L Aarden; S O Stapel; J M van Laar; P P Tak; G J Wolbink Journal: Ann Rheum Dis Date: 2009-07-12 Impact factor: 19.103
Authors: N L Berinstein; A J Grillo-López; C A White; I Bence-Bruckler; D Maloney; M Czuczman; D Green; J Rosenberg; P McLaughlin; D Shen Journal: Ann Oncol Date: 1998-09 Impact factor: 32.976
Authors: Divi Cornec; Brian F Kabat; John R Mills; Melissa Cheu; Amber M Hummel; Darrell R Schroeder; Matthew D Cascino; Paul Brunetta; David L Murray; Melissa R Snyder; Fernando Fervenza; Gary S Hoffman; Cees G M Kallenberg; Carol A Langford; Peter A Merkel; Paul A Monach; Philip Seo; Robert F Spiera; E William St Clair; John H Stone; David R Barnidge; Ulrich Specks Journal: Rheumatology (Oxford) Date: 2018-04-01 Impact factor: 7.580
Authors: Gitanjali Das; Vincent Damotte; Jeffrey M Gelfand; Carolyn Bevan; Bruce A C Cree; Lynn Do; Ari J Green; Stephen L Hauser; Riley Bove Journal: Neurol Neuroimmunol Neuroinflamm Date: 2018-03-19